Triazolam abuse

Limited results from clinical laboratory evaluations suggested that the GABAj l agonists zaleplon (Rush et al. 1999b) and Zolpidem (Rush et al. 1999a) produce effects that are consistent with abuse potential comparable to that of the benzodiazepine triazolam. The reported incidence of dependence on Zolpidem in the medical literature is low, compared with that for benzodiazepines, and is characterized by use of high doses, often in individuals with a history of substance abuse (Hajak et al. 2003 Vartzopoulos et al. 2000). 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

This non-BZD hypnotic, cyciopyrroione, is indicated for short-term management of insomnia. Zopiclone has a BZD-like profile, a short half-life of 3.5 to 6.5 hours, no active metabolites, minimal rebound effects, and less abuse potential than BZDs. The usual therapeutic dose is oral 7.5 mg administered 30 to 60 minutes before bedtime. Zopiclone has a well-documented capacity to reduce sleep latency, improve quality and duration of sleep, and reduce the frequency of nighttime awakenings. In clinical trials, 7.5 mg doses of zopiclone have been found to be as effective as triazolam 0.5 mg, temazepam 20 mg, flurazepam 15-30 mg, and nitrazepam 5 to 10 mg for the short-term treatment of insomnia (136). 

Zopiclone is relatively well tolerated (137). The most common adverse reaction is taste alteration. A postmarketing analysis of 10,000 cases revealed that zopiclone has a relatively low incidence of side effects (about 8%) (138). Like BZDs, zopiclone has a dose-related hangover effect (139). Rebound insomnia has occurred after short-term use (5 to 14 days) but does not appear to be as severe, even after abrupt withdrawal (140, 141). Abuse, tolerance, and physical and psychological dependence have been reported with zopiclone (142). Zopiclone has been shown to be as effective a hypnotic as triazolam in the elderly ( 143). More comparisons with short to medium half-life BZDs for the treatment of insomnia are needed to show that zopiclone has an advantage over the BZDs. 

Rush CR, Frey JM, Griffiths RR. Zaleplon and triazolam in humans acute behavioral effects and abuse potential. Psychopharmacology 1999 145 39-51. 

The abuse of benzodiazepine hypnotics (for example, Temazepam, Triazolam) by injection of the crushed tablets is of increasing concern, and these drugs can be used to lace supplies of street heroin and consequently they have a black market value. General prescribing habits need to be maintained to ensure some control of the abuse. 

Roache, J.D. and Griffiths, R.R., Diazepam and triazolam self-administration in sedative abusers concordance of subject ratings, performance and drug self-administration, Psychopharmacology, 99, 309, 1989. 

S toops, W.W. and Rush, C.R., Differential effects in humans after repeated administrations of zolpidem and triazolam, Am. J. Drug Alcohol Abuse, 29, 281, 2003. 

Rush, C.R., Madakasira, S., and Goldman, N.H., Acute behavioral effects of estazolam and triazolam in non-drug-abusing volunteers, Exp. Clin. Psychophatmacol., 4, 300, 1996. 

In a controlled study in healthy patients with a history of drug abuse, zaleplon was shown to have a comparable abuse potential to that of the benzodiazepine, triazolam [28]. 

Many benzodiazepines have potent hypnotic activity and are useful in the treatment of insomnia. Examples include flurazepam (Dalmane, A.93), midazolam (Versed, A.94), temazepam (Restoril, A.95), and triazolam (Halcion, A.96) (Figure A.28). Flunitrazepam (Rohypnol, A.97) is a particularly notorious sedative. Often called roofie or the date rape drug, flunitrazepam causes sedation and amnesia. Because of flunitrazepam s tendency to be abused, almost all nations tightly regulate the drug s availability. 

The acute effects of zolpidem and triazolam have been compared in 10 non-drug-abusing subjects using a Digit-... 

Tolerance to benzodiazepine hypnotic effects develops sooner with triazolam (after 2 weeks of continuous use) than with other benzodiazepine hypnotics." The hypnotic efficacy of flurazepam, quazepam, and temazepam is maintained for 1 month of continuous nightly use." Estazolam reportedly maintains the duration and quality of sleep at the maximum dosage (2 mg nightly) for up to 12 weeks." Long-term use (greater than 6 months) of benzodiazepines was associated with a low risk of abuse, side effects, and tolerance in patients with severe, chronic sleep disorders however, efficacy has not been established."... 

Pharmacologic treatment of RLS includes dopaminergic agents, benzodiazepines, opioids, or anticonvulsants. In mild cases of RLS, benzodiazepines may be first-line agents. Clonazepam, lorazepam, triazolam, and temazepam have been effective. Clonazepam 0.5 to 2 mg is most frequently studied. Opiates such as methadone 5 to 20 mg, codeine 30 to 120 mg, and oxycodone 2.5 mg are very effective, but the development of tolerance is a concern. Abuse potential with opiates is also a concern due to the chronic nature of the condition. Other agents that have been used include apomorphine, amantadine, tramadol, magnesium, oxycodone, propoxyphene, gabapentin, bromocriptine, clonidine, and carbamazepine. Tolerance may de-... 

Triazolam should be used cautiously in patients with impaired hepatic function, which prolongs elimination of the drug in elderly or debilitated patients, who are usually more sensitive to the drug s CNS effects and in individuals prone to addiction or drug abuse. 

A variety of allergic, hepatotoxic, and hematologic reactions to the benzodiazepines may occur, but the incidence is quite low these reactions have been associated with the use of flurazepam and triazolam but not with temazepam. Large doses taken just before or during labor may cause hypothermia, hypotonia, and mild respiratory depression in the neonate. Abuse by the pregnant mother can result in a withdrawal syndrome in the newborn. 

Roache, J. D., Griffiths, R. R. (1985). Comparison of triazolam and pentobarbital Performance impairment, subjective effects and abuse liability. The Journal of Pharmacology and Experimental Therapeutics, 234, 120-133. 

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